Phenylalanine, 4-chloro-, methyl ester → 2-[[[(Ethoxycarbonyl)amino]thioxomethyl]amino]-3-(4-chlorophenyl)-propionic acid methyl ester

HRID 2390605Notes

Reaction equation

HRID 2390605 reaction equation
[CH3:1][O:2][C:3](=[O:14])[CH:4]([NH2:13])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=1.C(N(C(C)C)CC)(C)C.[CH2:24]([O:26][C:27]([N:29]=[C:30]=[S:31])=[O:28])[CH3:25]>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:14])[CH:4]([NH:13][C:30]([NH:29][C:27]([O:26][CH2:24][CH3:25])=[O:28])=[S:31])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 26532Phenylalanine, 4-chloro-, methyl esterHCID 81531DiisopropylethylamineHCID 85320Ethyl isothiocyanatoformate

Product 1

HCID 592266732-[[[(Ethoxycarbonyl)amino]thioxomethyl]amino]-3-(4-chlorophenyl)-propionic acid methyl esterYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Methyl ester 1-1 (394 mg, 1.58 mmol) was dissolved in methylene chloride (4.0 mL) and diisopropylethylamine (0.82 mL, 4.73 mmol). The solution was cooled to 0° C. and ethoxycarbonyl isothiocyanate (0.21 mL, 1.73 mmol) was added dropwise. The mixture was allowed to warm to room temperature and was stirred 30 min. Methylene chloride (20 mL) was added, and the organic layer was washed with water (20 mL), 10% aqueous HCl (20 mL), and saturated brine (20 mL). The organic layer was dried with MgSO4, filtered and the solvent was removed in vacuo to yield the product as a yellow oil in 92% yield (502 mg, 1.45 mmol). 1H NMR (300 MHz, CDCl3): δ=10.10 (d, 1H, J=6.6 Hz), 8.11 (s, 1H), 7.27 (d, 2H, J=8.1 Hz), 7.10 (d, 2H, J=8.1 Hz), 5.25 (t, 1H, J=6.3 Hz), 4.23 (q, 2H, J=7.2 Hz), 3.73 (s, 3H), 3.32 (dd, 1H; J=14.1, 6.0 Hz), 3.20 (dd, 1H, J=13.8, 6.0 Hz), 1.30 (t, 3H, J=7.2 Hz); 13C NMR (75 mHz, CDCl3): δ=179.4, 170.8, 152.6, 134.2, 133.4, 130.8, 129.0, 63.2, 59.2, 53.6, 52.8, 36.8, 14.4; ESI-MS calcd for C14H17ClN2O4S [M+Na]+: 267.0495. found 267.0495.

Workup

  1. temperatureto warm to room temperature
  2. washthe organic layer was washed with water (20 mL), 10% aqueous HCl (20 mL), and saturated brine (20 mL)
  3. dry with materialThe organic layer was dried with MgSO4
  4. filtrationfiltered
  5. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-1704b91ca5ea4e6eb54bc55472111ced
Source dataset
uspto-grants-2012_09
Patent number
US08273778B2

Reaction notes

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